The long range objective of this proposed research project is to determine the functional properties of pulmonary vascular smooth muscle (VSM) and their alterations in pulmonary hypertension secondary to obstructive pulmonary disease and congenital cardiovascular disease (patent ductus arteriosis with right-to-left shunt). These studies will be conducted using a variety of pulmonary arteries from both extralobar and intralobar locations from canine and human subjects. These studies will investigate the relationship between function and composition in these tissues. a) Specimens in the form of intact cylindrical segments or helical strips will be studied in vitro under conditions of active (e.g., norepinephrine) and passive (2mM EGTA) smooth muscle. These data will be used to determine the effects of activation on stress-strain relations, and values of elastic properties and theoretical characteristic impedance. These results will be correlated with connective tissue and contractile protein content. b) the existence of the specific protein kinase and phosphatase which controls the degree of phosphorylation of myosin light chain in pulmonary VSM will be investigated. The role of factors such as Ca ion2, and cyclic nucleotides in the regulation of this phosphorylation-dephosphorylation system will be studied. c) The actin-activated ATPase activity of pulmonary VSM myosin and its regulation via phosphorylation, Ca ion2 concentration and tropomyosin will be investigated. Furthermore, the relationship between myosin light chain phosphorylation and VSM force development will be correlated. d) Studies will be conducted to determine the mechanics of pulmonary VSM cells in these tissues including the properties of series elasticity and force-velocity-length relations. These studies will be correlated with chemical composition including water and electrolytes as well as myosin ATPase activity. e) The alterations in these properties associated with pulmonary hypertension will be assessed along with their reversibility with treatment.